Cytosolic sulfotransferase superfamilies (SULTs) act on a wide variety of natural and synthetic chemicals. With the wide tissue distribution, extensive substrate affinity, involvement in the detoxification and metabolism of numerous drug compounds, hormones and xenobiotics, and the participation in the bioactivation of environmental and dietary procarcinogens, the SULT1A1 gene has been the most widely studied. Glatt (2000) Chem. Biol. Interact. 129(1-2):141-170.
SULT1A1 is one of four SULT1A genes located on chromosome 16 that share at least 93% amino acid sequence identity. Her et al. (1996) Genomics 33(3): 409-20; Raftogianis et al. (1996) Pharmacogenetics 6(6): 473-87; and Hildebrandt et al. (2004) Biochem. Biophys. Res. Commun. 321(4): 870-8. Three non-synonymous single nucleotide polymorphisms (SNPs) divide the SULT1A1 gene into four alleles: SULT1A1*1 (wildtype), SULT1A1*2 (Arg213His), SULT1A1*3 (Met223Val), and SULT1A1*4 (Arg37Gln). The two most common alleles found among most populations are the 1A1*1 and 1A1*2 alleles. Subjects homozygous for 1A1*2 are thought to have an 85% reduction in platelet phenol sulfotransferase activity and a decrease in thermal stability compared to subjects that are heterozygous for 1A1*1/1A1*2 or homozygous for 1A1*1. See Raftogianis et al. (1997) Biochem. Biophys. Res. Commun., 239(1):298-304; and Raftogianis et al. (1999) Biochem. Pharmacol., 58(4):605-16.
Langsenlehner et al. (2004, Breast Cancer Res. Treat., 87(1):19-22) showed that in their breast cancer population, the 1A1*2 allele was associated with lymph node metastasis but not with breast cancer itself. Saintot et al. (2003, Int. J. Cancer, 107(4):652-7) also found no association of the 1A1*2 allele to breast cancer in the population they studied; however they observed that the 1A1*2 allele increased the risk for breast cancer if one smoked. Within a Chinese population, the frequency of the 1A1*2 allele in women with breast cancer was statistically significant compared to a control set. Han et al. (2004) Toxicol. Lett., 150(2):167-77. Conversely, in other studies, the 1A1*1 allele may be associated with prostate and bladder cancer. Nowell et al. (2004) Cancer Epidemiol. Biomarkers Prev., 13(2):270-6; and Zheng et al. (2003) Cancer Lett., 202(1):61-9. Based on these variable results, other factors may play a critical role in SULT1A1's function and involvement with certain types of cancers.